ACUTE KIDNEY INJURY IN SEVERE PNEUMONIA ASSOCIATED WITH COVID-19

The clinical and epidemiological features of acute kidney injury in severe and extremely severe pneumonia associated with coronavirus disease-2019 (COVID-19) are considered. An observational prospective study was conducted with the inclusion of 117 patients, including 75 men and 42 women, suffering from severe and extremely severe pneumonia associated with COVID-19, who were treated in the intensive care unit of the 1586th Military Clinical Hospital in 2020–2022. Acute kidney injury was diagnosed in 21 (17.9%) patients (stage 1 in 10, stage 2 in 4, and stage 3 in 7 patients), kidney dysfunction was recorded in 22 (8.8%) patients (serum creatinine was higher than normal, but does not reach the diagnostic criteria of Kidney Disease Improving Global Outcomes). Four patients underwent renal replacement therapy. The probability of kidney damage increases with age (the average age of the patients with acute kidney damage is 65 (58;71) years, and those without acute kidney damage was 47.5 (41;55) years;p = 0.0001). Compared with patients without acute kidney injury, patients with acute kidney injury scored higher on the scales NEW (p = 0.000975), SMRT-CO (p = 0.011555), and Sequential Organ Failure Assessment (p = 0.000042). Among those suffering from acute kidney injury, significantly more pronounced manifestations of systemic inflammation were determined (leukocytes, p = 0.047324;platelets, p = 0.001230;ferritin, p = 0.048614;and D-dimer, p = 0.004496). In the general cohort, the mortality rate was 22.2%, whereas a significant intergroup difference in mortality was observed, i.e., 52.4% in patients with acute kidney injury and 15.62% in those without acute kidney injury (Chi-squared criterion, 13.468;p < 0.001). Invasive artificial lung ventilation was performed in 19.66% of the patients, and a significant intergroup difference was identified, with 66.7% in patients with acute kidney injury and 9.38% in patients without acute kidney injury (Chi-squared criterion, 35.810;p < 0.001). The durations of treatment in the intensive care unit in patients with and without acute kidney injury were 9 (7;14) and 6 (4;10) days, respectively. After the treatment, all patients with acute kidney injury had fully recovered kidney function upon discharge. In general, acute kidney injury occurs in almost every fifth patient with severe and extremely severe pneumonia associated with COVID-19, aggravates the condition of patients, and increases mortality. The alertness of doctors regarding acute kidney injury and early diagnosis and timely nephroprotective treatment may reduce the possibility of adverse disease outcomes. All rights reserved © Eco-Vector, 2022.

Near-infrared photobiomodulation therapy for rehabilitation of patients with long COVID

About 80% of the patients recovering from COVID-19 have inflammation symptoms, like brain fog, myopathy, myalgia, muscle weariness, headache, mental tiredness, asthenia, adynamia, dizziness, tinnitus, hearing loss, telogenic effluvium and mood disturbances. Here, we demonstrate how transcranial and systemic photobiomodulation using near-infrared LEDs emitting 850 nm wavelength light enhanced cognition and reduced pain. Participants were separated into transcranial photobiomodulation with near-infrared LEDs (850 nm, 10W, 10 minutes), photobiomodulation with a punctual cutaneous application (850nm, 10W, 10-40 minutes), and both treatments. All patients underwent 10-day treatments at least. © 2023 SPIE.

Mitochondrial N-formyl methionine peptides contribute to exaggerated neutrophil activation in patients with COVID-19.

Neutrophil dysregulation is well established in COVID-19. However, factors contributing to neutrophil activation in COVID-19 are not clear. We assessed if N-formyl methionine (fMet) contributes to neutrophil activation in COVID-19. Elevated levels of calprotectin, neutrophil extracellular traps (NETs) and fMet were observed in COVID-19 patients (n = 68), particularly in critically ill patients, as compared to HC (n = 19, p < 0.0001). Of note, the levels of NETs were higher in ICU patients with COVID-19 than in ICU patients without COVID-19 (p < 0.05), suggesting a prominent contribution of NETs in COVID-19. Additionally, plasma from COVID-19 patients with mild and moderate/severe symptoms induced in vitro neutrophil activation through fMet/FPR1 (formyl peptide receptor-1) dependent mechanisms (p < 0.0001). fMet levels correlated with calprotectin levels validating fMet-mediated neutrophil activation in COVID-19 patients (r = 0.60, p = 0.0007). Our data indicate that fMet is an important factor contributing to neutrophil activation in COVID-19 disease and may represent a potential target for therapeutic intervention.

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

A systematic review on immunity functionalities and nutritional food recommendations to develop immunity against viral infection

Immunity plays a fundamental role in the maintenance and protection of the human body from infectious and pathogenic microorganisms. It requires regular intake of nutrients for proper functioning of the immune system. Due to an unbalanced lifestyle and consumption of ready-to-eat foods, immunity is being affected negatively. Inflammation and immunity are influenced by diet and nutrition. Simple sugars, trans fats, refined carbs, and processed meat, among other meals, may induce inflammation while simultaneously counteracting the anti-inflammatory benefits of omega-3 fatty acids. As a result, unhealthy food intake may enhance systemic inflammation in individuals, boosting the generation of IL-6. Dietary nutrition is a well-known aspect of immune system maintenance, with the significance of micronutrients prominently featured in a variety of scientific literary works. Currently, global population is susceptible viral infection such as COVID-19. This viral strain is directly attacking the immunity of the individual and bringing it at risk. When a patient's immune system isn't operating correctly, COVID-19 is thought to raise the harshness of the infection or make it more vulnerable to contagious diseases. This review paper will help in understanding the immune responses mechanism along with diet balance and maintaining the sufficiency of vitamins and minerals to fight against COVID-19 infection.Copyright © 2023 The Author(s)

The modified systemic inflammation score is a predictor of ICU admission of COVID-19 patients

Objective: To evaluate the effect of the modified systemic inflammation score (mSIS) on prognosis in patients diagnosed with COVID-19. Method(s): In this retrospective cross-sectional study, 181 patients were selected and divided into two groups: patients with and without admission to the intensive care unit (ICU). An albumin level of >=4.0 g/dL and lymphocyte-to-monocyte ratio (LMR) of >=3.4 was scored 0, an albumin level of <4.0 g/dL or LMR of <3.4 was scored 1, and an albumin level of <4.0 g/dL and LMR of <3.4 was scored 2. Result(s): A total of 242 COVID-19 positive patients were initially included in this study. Of these patients, 61 were excluded and 181 patients remained. Among the 181 participants, 94 (51.9%) were female, and the median age was 61 (51, 75) years. The mSIS scale ranged from 0 to 2. After analysis, the median score was 0 (0, 0) in the non-ICU group and 2 (0, 2) in the ICU group (P<0.001). The median white blood cell, lymphocyte counts, and albumin levels were lower in the ICU group (P<0.001, P<0.001, and P<0.001, respectively). In logistic regression analysis lymphocytopenia (OR=5.158, 95% CI=1.249-21.304, P=0.023), hypoalbuminemia (OR=49.921, 95% CI=1.843-1 352.114, P=0.020), AST elevation (OR=3.939, 95% CI=1.017-15.261, P=0.047), and mSIS=2 (OR=5.853, 95% CI=1.338-25.604, P=0.019) were identified as independent predictors of ICU admission. Conclusion(s): The mSIS can be used as an independent parameter for establishing the intensive care needs of patients with COVID-19.Copyright © 2023 Authors. All rights reserved.

Laboratory characteristics of cytokine storm syndrome in COVID-19 infection

In COVID-19, pneumonia develops simultaneously with cytokine storm syndrome (CSS). A number of cytokines and inflammation parameters were measured in 226 patients with COVID-19 pneumonia (median lung involvement of 60%) and 36 COVID-19 related deaths, during first wave of epidemic. The comparison group consisted of 49 MAS and 52 SS fatal cases, collected, retrospectively. Profile of cytokines and laboratory biomarkers in lethal COVID-19 cases resembled both pathologies, but in COVID-19 it was distinguished by high NLR/IL-6 and low IFN-γ/TNF-α. The new CSS score integrated serum levels of IL-6, IL-10, IL-18, and PCT, giving a range of 0-4 points for each biomarker, and sum from 0 to 12 points. Over five points indicated higher risk of unfavorable outcome. CSS score was validated on separate cohort of 121 patients. Surprisingly CSS parameters were higher in patients of risk groups (older and comorbid). Integrated CSS score can predict severe cases of COVID-19 disease. © 2023 Elsevier Inc. All rights reserved.

Cardiac Arrhythmias in Post-COVID Syndrome: Prevalence, Pathology, Diagnosis, and Treatment.

An increase in post-COVID patients with late sequelae of acute COVID-19 infection is emerging as an ongoing challenge for physicians and healthcare professionals. Since the beginning of the pandemic, it has rapidly become evident that the acute infection is not limited to the respiratory tract but that several organs, including the cardiovascular system, can be affected. Moreover, in a significant proportion of patients (ranging from about 10 to up to 50%) with former COVID-19, cardiopulmonary symptoms such as dyspnea, palpitations, restricted physical capacity, and cardiac arrhythmias can persist weeks and months after the acute SARS-CoV-2 infection. The spectrum of COVID-19-associated arrhythmias is rather wide, most likely due to various pathomechanisms. In this article, the prevalence of cardiac arrhythmias and underlying pathologies are reviewed, including direct myocardial injury and abnormal consequences with an impact on cardiac electric instability. The hyperinflammatory reaction of the host immune system is specifically considered. Moreover, several distinct rhythm disorders occurring in post-COVID patients are discussed with regard to their clinical management.

Aggregate index of systemic inflammation (AISI) in admission as a reliable predictor of mortality in COPD patients with COVID-19.

BACKGROUND: The role of leukocytes and systemic inflammation indicators in predicting the severity and mortality of inflammatory diseases has been well reported, such as the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), neutrophil/lymphocyte*platelet ratio (NLPR), derived neutrophil/lymphocyte ratio (dNLR), aggregate index of systemic inflammation (AISI), as well as systemic inflammation response index (SIRI) and systemic inflammation index (SII). The purpose of the present study was to investigate the prognostic role of systemic inflammatory indicators in the mortality of chronic obstructive pulmonary disease (COPD) patients with COVID-19. METHODS: This retrospective study included 169 COPD patients hospitalized with COVID-19. Demographic, clinical, and laboratory data were obtained from the patients' electronic records. The ability of systemic inflammation indeces to distinguish the severity of COVID-19 was determined by receiver operating characteristic (ROC) analysis, and survival probability was determined by the mean of Kaplan-Meier curves, with the endpoint being death. RESULTS: ROC curves showed that the AUD level was significant for WBC, MLR, SIRI, and AISI. Interestingly, Kaplan-Meier survival curves revealed that survival was lower with higher MLR (HR = 2.022, 95% CI = 1.030 to 3.968, P < 0.05) and AISI (HR = 2.010, 95% CI = 1.048 to 3.855, P < 0.05) values. However, the multivariate Cox regression model showed that only AISI was significantly associated with survival. CONCLUSION: AISI in COPD patients with COVID-19 was a reliable predictor of mortality.

Vitronectin promotes immunothrombotic dysregulation in the venular microvasculature.

Microvascular immunothrombotic dysregulation is a critical process in the pathogenesis of severe systemic inflammatory diseases. The mechanisms controlling immunothrombosis in inflamed microvessels, however, remain poorly understood. Here, we report that under systemic inflammatory conditions the matricellular glycoproteinvitronectin (VN) establishes an intravascular scaffold, supporting interactions of aggregating platelets with immune cells and the venular endothelium. Blockade of the VN receptor glycoprotein (GP)IIb/IIIa interfered with this multicellular interplay and effectively prevented microvascular clot formation. In line with these experimental data, particularly VN was found to be enriched in the pulmonary microvasculature of patients with non-infectious (pancreatitis-associated) or infectious (coronavirus disease 2019 (COVID-19)-associated) severe systemic inflammatory responses. Targeting the VN-GPIIb/IIIa axis hence appears as a promising, already feasible strategy to counteract microvascular immunothrombotic dysregulation in systemic inflammatory pathologies.

Towards a Better Understanding of the Complexities of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Long COVID.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex condition arising in susceptible people, predominantly following viral infection, but also other stressful events. The susceptibility factors discussed here are both genetic and environmental although not well understood. While the dysfunctional physiology in ME/CFS is becoming clearer, understanding has been hampered by different combinations of symptoms in each affected person. A common core set of mainly neurological symptoms forms the modern clinical case definition, in the absence of an accessible molecular diagnostic test. This landscape has prompted interest in whether ME/CFS patients can be classified into a particular phenotype/subtype that might assist better management of their illness and suggest preferred therapeutic options. Currently, the same promising drugs, nutraceuticals, or behavioral therapies available can be beneficial, have no effect, or be detrimental to each individual patient. We have shown that individuals with the same disease profile exhibit unique molecular changes and physiological responses to stress, exercise and even vaccination. Key features of ME/CFS discussed here are the possible mechanisms determining the shift of an immune/inflammatory response from transient to chronic in ME/CFS, and how the brain and CNS manifests the neurological symptoms, likely with activation of its specific immune system and resulting neuroinflammation. The many cases of the post viral ME/CFS-like condition, Long COVID, following SARS-CoV-2 infection, and the intense research interest and investment in understanding this condition, provide exciting opportunities for the development of new therapeutics that will benefit ME/CFS patients.

Role of prebiotic dietary fiber in periodontal disease: A systematic review of animal studies.

Background: Periodontitis is a chronic inflammatory condition affecting the supporting structures of a tooth in the oral cavity. The relationship between dietary fiber and periodontitis is poorly understood. The objective of this systematic review is to investigate if an intake of dietary fiber modulates periodontal disease in animal models and any concomitant effects on systemic inflammation, microbiota and their metabolites. Methods: Animal studies using periodontitis models with any form of fiber intervention were included. Studies with comorbidities that were mutually inclusive with periodontitis and animals with physiological conditions were excluded. Search strategy with MeSH and free-text search terms were finalized and performed on the 22nd of September 2021.CINAHL Complete, EMBASE, MEDLINE, SciVerse Scopus® and Web of Science Core Collection databases were used to identify studies. SYRCLE's risk of bias tool and CAMARADES were used for quality assessment. Results were synthesized utilizing Covidence© web-based platform software to remove duplicates, and the remaining studies were manually filtered. Results: A total of 7,141 articles were retrieved from all databases. Out of 24 full-text articles assessed for eligibility, four studies (n = 4) were included. Four studies involved the use of ß-(1,3/1,6)-glucan (n = 3) and mannan oligosaccharide (n = 1) at differing dosages for different study durations. All studies utilized a ligature-induced model of periodontitis in rats, either Wistar (n = 3) or Sprague-Dawley (n = 1). A dose-dependent relationship between the increased fiber intake and decrease in alveolar bone loss and pro-inflammatory markers was observed. Conclusion: The number of included studies is limited and narrow in scope. They highlight the importance of pre-clinical trials in this field with broader dietary fiber intervention groups before proceeding to clinical trials. The use of dietary fiber as an intervention shows promise in the reduction of inflammatory conditions like periodontitis. However, further research is required to delineate the relationship between diet and its effects on microbiota and their metabolites such as short chain fatty acids in animal models of periodontitis.

The Outcome of COVID-19 Infection in Patients With Gastrointestinal Diseases: An Experience at a Tertiary Center.

OBJECTIVE: Observing the impact of the coronavirus disease 2019 (COVID-19) pandemic on digestive diseases in hospitalized patients at the Department of Gastroenterology-Hepatology in "Mother Teresa" University Hospital Center (UHC),Tirana. METHODS: This retrospective study was carried out from June 2020 to December 2021 involving 41 cases of patients >18 years who were positive for COVID-19 infection detected by RT-PCR (Reverse Transcription-Polymerase Chain Reaction) assays of nasopharyngeal swab specimens. The severity of COVID-19 infection was evaluated by hematological/biochemical parameters, blood oxygenation/need for oxygen, radiological data on pulmonary CT imaging. RESULTS: Out of 2527 hospitalized cases, 1.6% (41) were positive for the infection. The average age was 60.05 +/- 15.008 years. The group of age with more patients (48.8%) was 41-60 years. Infected males were higher than females (p<0.001). Out of the total, 21% were vaccinated at the diagnosis. Most patients came from urban areas, more than a half from the capital. Frequency of the digestive diseases was: cirrhosis 31.7%, pancreatitis 21.9%, alcoholic liver disease 21.9%, gastrointestinal hemorrhage 19.5%, digestive cancer 14.6%, biliary diseases 7.3%, inflammatory bowel disease (IBD) 2.4%, other digestive diseases 4.8%. Fever (90%) and fatigue (78.04%) were the dominant clinical signs.  Biochemical and hematological parameters showed elevation of average value of aspartate amino transferase (AST), alanine transaminase (ALT) (AST>ALT, p<0.001), and bilirubin in all the patients. Higher levels of creatinine and significantly predictive value of systemic inflammation indices NLR (neutrophil to lymphocyte ratio ) and MLR (monocyte to lymphocyte ratio) were found in the fatality cases. Patients with cirrhosis had more severe form of COVID-19, lower blood oxygenation and needed treatment by O2-therapy (p<0.046). Death rate was 12%. A strong correlation was found between the need for O2-therapy and deaths (p<0.001) and between characteristic findings for COVID-19 in pulmonary CT imaging and low blood oxygenation (p<0.003). CONCLUSION: Comorbidity with chronic diseases, such as liver cirrhosis, has an important impact on the severity and mortality of the patients with COVID-19 infection. Inflammatory indices, such as NLR (neutrophil to lymphocyte ratio) and MLR (monocyte to lymphocyte ratio), are useful tools in predicting the evolution toward severe forms of the disease.

Causal associations and shared genetics between hypertension and COVID-19.

To evaluate the genetic relationship between hypertension and COVID-19 and explore the molecular pathways linking hypertension to COVID-19. We performed genetic correlation and Mendelian randomization (MR) analyses to assess potential associations between hypertension and hospitalized COVID-19. We compared genome-wide association signals to reveal shared genetic variation between hypertension and hospitalized COVID-19. Moreover, hypertension-driven molecular pathways were constructed based on large-scale literature data to understand the influence of hypertension on COVID-19 at the molecular level. Hypertension has a positive genetic correlation with COVID-19 (rg = 0.19). The MR analyses indicate that genetic liability to hypertension confers a causal effect on hospitalized COVID-19 (odds ratio [OR]: 1.05, confidence interval [CI]: 1.00-1.09, p = 0.030). Hypertension and hospitalized COVID-19 have three overlapping loci and share eight protein-coding risk genes, including ABO, CSF2, FUT2, IZUMO1, MAMSTR, NPNT, RASIP1, and WNT3. Molecular pathway analysis suggests that hypertension may promote the development of COVID-19 through the induction of inflammatory pathways. Our study suggests that genetically determined hypertension may increase the risk for severe COVID-19. The shared genetic variation and the connecting molecular pathways may underline causal links between hypertension and COVID-19.

A case of fatal multi-organ inflammation following COVID-19 vaccination.

A 14-year-old Japanese girl died unexpectedly 2 days after receiving the third dose of the BNT1262b2 mRNA COVID-19 vaccine. Autopsy findings showed congestive edema of the lungs, T-cell lymphocytic and macrophage infiltration in the lungs, pericardium, and myocardium of the left atria and left ventricle, liver, kidneys, stomach, duodenum, bladder, and diaphragm. Since there was no preceding infection, allergy, or drug toxicity exposure, the patient was diagnosed with post-vaccination pneumonia, myopericarditis, hepatitis, nephritis, gastroenteritis, cystitis, and myositis. Although neither type of inflammation is fatal by itself, arrhythmia is reported to be the most common cause of death in patients with atrial myopericarditis. In the present case, arrhythmia of atrial origin was assumed as the cause of cardiac failure and death. In sudden post-vaccination deaths, aggressive autopsy systemic search and histological examination involving extensive sectioning of the heart, including the atrium, are indispensable.

The Impact of the Association between Periodontitis and Coronavirus Disease Infection on Oral and Systemic Complications. Review

Several risk factors have been associated with severe coronavirus disease and include factors such as advanced age and sex (male) and comorbidities such as obesity and the presence of underlying diseases (eg, hypertension, cardiovascular disease, cerebrovascular disease, chronic kidney disease, and diabetes). These predisposing conditions share several standard features that could explain why they are associated with worse disease outcomes. Persistent and uncontrolled inflammation is a key manifestation of several diseases, such as periodontitis, cardiovascular diseases, neurodegenerative diseases, diabetes, and coronavirus disease infection. The oral cavity is a reservoir for respiratory pathogens, especially among patients with poor oral hygiene and periodontitis, and dysregulated inflammatory and immune response. In fact, periodontal pockets in the elderly have been associated with increased risk of mortality from pneumonia, and periodontitis patients are more likely to develop hospital -acquired, pneumonia than healthy ones are.Conclusions;Periodontitis shares several common features with coronavirus disease including similarities in comorbidities and effects on systemic inflammation. However, further research would be needed to confirm these hypotheses.

First-Generation College Students, Emotional Support, and Systemic Inflammation Following the College Transition.

PURPOSE: To examine whether emotional support moderates the association between college generation status and concurrent and prospective levels of systemic inflammation during the college transition among a sample of older U.S. adolescents. METHODS: At an undergraduate tertiary institution, 41 first-generation college students (first-gens) and 46 continuing-generation college students (continuing-gens) in their first semester of college reported on basic demographic information and perceived emotional support. They also had their blood drawn midway through both the first and second semester to measure C-reactive protein and interleukin-6. An inflammatory composite for each semester was created by averaging the standardized scores for log-transformed C-reactive protein and interleukin-6. RESULTS: Compared to continuing-gens, first-gens had greater systemic inflammation in the first semester regardless of their level of emotional support (B = 0.515, p = .003). However, emotional support moderated the association between college generation status and prospective systemic inflammation in the second semester (B = -0.525, p = .007) such that first-gens had greater systemic inflammation compared to continuing-gens, but only if they reported lower levels of emotional support (B = 0.826, p = .002). This moderation effect held after further adjusting for systemic inflammation in the first semester (B = -0.374, p = .022). Also discussed are results of secondary analyses examining sources of support. DISCUSSION: Compared to continuing-gens, first-gens had greater systemic inflammation in the first semester irrespective of emotional support, suggesting all first-gens may stand to benefit from college resources provided early in the college transition. Furthermore, first-gens who reported lower levels of emotional support may benefit from additional college resources provided beyond the first semester.

Serial Changes in Blood-Cell-Count-Derived and CRP-Derived Inflammatory Indices of COVID-19 Patients.

The aim of the study was to investigate the serial changes in inflammatory indices derived from blood cell counts and C-reactive protein (CRP) levels in COVID-19 patients with good and poor outcomes. We retrospectively analyzed the serial changes in the inflammatory indices in 169 COVID-19 patients. Comparative analyses were performed on the first and last days of a hospital stay or death and serially from day 1 to day 30 from the symptom onset. On admission, non-survivors had higher CRP to lymphocytes ratio (CLR) and multi-inflammatory index (MII) values than survivors, while at the time of discharge/death, the largest differences were found for the neutrophil to lymphocyte ratio (NLR), systemic inflammation response index (SIRI), and MII. A significant decrease in NLR, CLR, and MII by the time of discharge was documented in the survivors, and a significant increase in NLR was documented in the non-survivors. The NLR was the only one that remained significant from days 7-30 of disease in intergroup comparisons. The correlation between the indices and the outcome was observed starting from days 13-15. The changes in the index values over time proved to be more helpful in predicting COVID-19 outcomes than those measured on admission. The values of the inflammatory indices could reliably predict the outcome no earlier than days 13-15 of the disease.

Efficacy and safety of the investigational complement C5 inhibitor zilucoplan in patients hospitalized with COVID-19: an open-label randomized controlled trial.

BACKGROUND: The efficacy and safety of complement inhibition in COVID-19 patients is unclear. METHODS: A multicenter randomized controlled, open-label trial. Hospitalized COVID-19 patients with signs of systemic inflammation and hypoxemia (PaO2/FiO2 below 350 mmHg) were randomized (2:1 ratio) to receive standard of care with or without the C5 inhibitor zilucoplan daily for 14 days, under antibiotic prophylaxis. The primary outcome was improvement in oxygenation at day 6 and 15. RESULTS: 81 patients were randomly assigned to zilucoplan (n = 55) or the control group (n = 26). 78 patients were included in the safety and primary analysis. Most were men (87%) and the median age was 63 years. The mean improvement in PaO2/FiO2 from baseline to day 6 was 56.4 mmHg in the zilucoplan group and 20.6 mmHg in the control group (mean difference + 35.8; 95% confidence interval (CI) - 9.4 to 80.9; p = 0.12), an effect also observed at day 15. Day 28 mortality was 9% in the zilucoplan and 21% in the control group (odds ratio 0.4; 95% CI 0.1 to 1.5). At long-term follow up, the distance walked in a 6-min test was 539.7 m in zilucoplan and 490.6 m in the control group (p = 0.18). Zilucoplan lowered serum C5b-9 (p < 0.001) and interleukin-8 (p = 0.03) concentration compared with control. No relevant safety differences between the zilucoplan and control group were identified. CONCLUSION: Administration of zilucoplan to COVID-19 patients in this proof-of-concept randomized trial was well tolerated under antibiotic prophylaxis. While not reaching statistical significance, indicators of respiratory function (PaO2/FiO2) and clinical outcome (mortality and 6-min walk test) suggest that C5 inhibition might be beneficial, although this requires further research in larger randomized studies.

Cardiovascular Risk Score and Pulmonary Gas Exchange in COVID-19 Patients Show No Correlation.

BACKGROUND: COVID-19 induces robust systemic inflammation. Patients with cardiovascular disease (CVD) are at an increased risk of death. However, much effort is being spent to identify possible predictors of negative outcomes in order to have a more specific clinical setting. CVD scores are a useful tool in evaluating risk of cardiovascular events. AIM: We evaluated oxygenation and characteristics in COVID-19 patients according to cardiovascular risk stratification performed using the Framingham risk score (FRS) for cardiovascular disease. MATERIALS AND METHODS: We evaluated 155 COVID-19 patients (110 males and 45 females, aged 67.43 ± 14.72 years). All patients underwent a complete physical examination, chest imaging, laboratory tests and blood gas analysis at the time of diagnosis. Seventeen patients died (10 males and 7 females, aged 74.71 ± 7.23 years) while the remaining 138 patients (100 males and 38 females, aged 66.07 ± 15.16 years) were alive at discharge. RESULTS: Deceased patients have an increased FRS compared to those that survived (27.37 ± 5.03 vs. 21.33 ± 9.49, p < 0.05). Compared to survivors, the deceased group presents with a significant increase in white blood cells (p < 0.05) and D-dimers (p < 0.05). There was no difference in pCO2, SO2, and in alveolar arteriolar oxygen difference (A-aDO2). On the contrary, in deceased patients there was an increased pO2 (p < 0.05) and a decreased ratio between oxygen inspired and pO2 (P/F; p < 0.05). FRS shows a negative correlation to P/F (r = 0.42, p < 0.05) in the deceased while no correlation was found in the survivors. No other correlation has been found with blood gas parameters or in the inflammation parameters evaluated in the two groups. DISCUSSION: CVD may be considered as a major risk factor for death in COVID-19 patients. The increased risk relates to a reduced lung capacity but it is not related to blood gas values. Similarly, CV risk score results are independent from the inflammatory status of the patients.